title: Non-Hodgkin lymphoma risk and variants in genes controlling lymphocyte development.
abstract: Non-Hodgkin lymphomas (NHL) are a heterogeneous group of solid tumours of lymphoid cell origin. Three important aspects of lymphocyte development include immunity and inflammation, DNA repair, and programmed cell death. We have used a previously established case-control study of NHL to ask whether genetic variation in genes involved in these three important processes influences risk of this cancer. 118 genes in these three categories were tagged with single nucleotide polymorphisms (SNPs), which were tested for association with NHL and its subtypes. The main analysis used logistic regression (additive model) to estimate odds ratios in European-ancestry cases and controls. 599 SNPs and 1116 samples (569 cases and 547 controls) passed quality control measures and were included in analyses. Following multiple-testing correction, one SNP in MSH3, a mismatch repair gene, showed an association with diffuse large B-cell lymphoma (OR: 1.91; 95% CI: 1.41-2.59; uncorrected p = 0.00003; corrected p = 0.010). This association was not replicated in an independent European-ancestry sample set of 251 diffuse large B-cell lymphoma cases and 737 controls, indicating this result was likely a false positive. It is likely that moderate sample size, inter-subtype and other genetic heterogeneity, and small true effect sizes account for the lack of replicable findings.
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Schuetz
authors.forename: Denise
authors.initials: D
authors.lastname: Daley
authors.forename: Stephen
authors.initials: S
authors.lastname: Leach
authors.forename: Lucia
authors.initials: L
authors.lastname: Conde
authors.forename: Brian R
authors.initials: BR
authors.lastname: Berry
authors.forename: Richard P
authors.initials: RP
authors.lastname: Gallagher
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Paige M
authors.initials: PM
authors.lastname: Bracci
authors.forename: Christine F
authors.initials: CF
authors.lastname: Skibola
authors.forename: John J
authors.initials: JJ
authors.lastname: Spinelli
authors.forename: Angela R
authors.initials: AR
authors.lastname: Brooks-Wilson
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008214:Lymphocytes / Q000166:cytology*; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology* / Q000235:genetics*; D000074081:MutS Homolog 3 Protein; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C078444:MSH3 protein, human; D000074081:MutS Homolog 3 Protein